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Is Measles Vaccine a Marker for Better Preventive Health Care
- Craig Dalton (2 July 1999)
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Who brought measles?
- Tomas Engler (6 July 1999)
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Measles immunisation
- Clinton Buckoke (8 July 1999)
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Measles vaccination and the declining incidence of esotropia
- Robin Finlay (8 July 1999)
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Socioeconomic confounding may also play a role
- David Emerton (20 July 1999)
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Measles immunisation and socioeconomic confounding
- Frank Shann (20 August 1999)
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Craig Dalton, Director Hunter Public Health Unit
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The hypotheis that measles immunisation provides nonspecific immune stimulation sufficient to decrease mortality from other diseases is interesting. However, I don't really believe the studies have ruled out the more likely explanation that measles immunisation is just a marker for other socioculturally determined health seeking behaviours. The fact that similar effects are not seen for other vaccines does not exclude measles immunisation from being correlated with health seeking behaviours. Measles vaccination is different to other vaccines - in its timing and it is often associated with national campaigns (including in some of the studies Dr Shann references). Are there any data that rules out the confounding effect of sociocultural determinants? |
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Tomas Engler, Senior Health Specialist Inter-American Development Bank
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History has documented well for us the devastating effects of the arrival of the measles virus from Europe several centuries ago (e.g., Iceland and the Americas). Some will also remember that when measles vaccine became available on a large scale (late 60's), in the unpublished and published experience (1970's) of a number of clinicians, the relationship between measles and susceptibility to other diseases, notably tuberculosis, was well established, at least in Amerindian and other population groups living in poverty and not exposed to measles prior to outbreaks recorded at the time. Studies published then documenting effects of clinical measles on the immune response were accepted as a reasonable explanation. Thus, Dr. Shann's editorial, while no surprise, comes as a welcome reminder of things forgotten. The implications for public health action are clear - and not unrelated to the relationship between AIDS and susceptibility to other diseases, which has cost so much money to "prove". The point is one of public policy: how to maintain funding for successful epidemiological activities once their goal has been attained (in this case, the elimination or eradication of measles, hopefully just around the corner). The history of tuberculosis control, while somewhat "glorious" during the post-World War II years related to strong social support (NGO sales of stamps), has been a glaring example of successive failures in establishing political priority for what once was the "disease of kings". It is only fair to recognize the renewed efforts being made by WHO over the past 4 or 5 years, and the commitment expressed by their new Director General in this regard. Unfortunately, the national response has yet to materialize in the intensity and perspective required. More realistic approaches need to be developed which take into account the financial and logistic barriers still limiting access to general healthcare across the globe. Although it is true that our most successful ventures have been in the pursuit of one creature at a time (i.e., yellow fever, smallpox, polio), how can we deal effectively with the long and growing list on the table? While there are many reasons to be optimistic, lip service to these causes - and to their integration to the mainstream of primary healthcare - is not enough. How long do we need to wait and how big a price should we all pay for the consequences of our inertia? Have we learned the lessons from our failure in controlling the AIDS epidemic in its early stages? Are we really ready for another Ebola? Or is this just a love affair with Mycobacteriae and other creatures that share our planet and our bodies? Do we really care at all? |
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Clinton Buckoke
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Editor I have just read the fourth editorial in today's BMJ (1) on measles immunisation, and was interested to learn that "the vaccine itself may reduce mortality from conditions other than measles." I have read the rest of the article and it is not clear whether the reduction in mortality is from: a) all conditions other than measles b) all infective conditions other than measles c) specific infective conditions other than measles d) specific non-infective conditions other than measles Although I work as a hospital specialist, I enjoy the BMJ as a generalist as it is a great help in keeping my knowledge-base broad. Perhaps your contributor could have been more specific for the sake of those readers who do not have the time to seek out all the articles by Aaby and his numerous co-workers. Clinton Buckoke Consultant Anaesthetist Southend Hospital Westcliff-on-Sea Essex SS0 0RY 1 Shann F, A little bit of measles does you good. BMJ 1999;319:4-5 |
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Robin Finlay
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Frank Shann's editorial 'A little bit of measles does you good' (1) highlights several unexpected effects of mass measles vaccination. No more satisfactory explanation has been advanced for an apparently marked decline in the incidence of childhood esotropia (convergent squint) than that it may be due to a large reduction in the incidence of measles. Figures for the incidence of childhood esotropia, with a peak at age 3 to 4 years, are difficult to gather, but there is general agreement that fewer cases present in the United Kingdom than a generation ago. More easily verified is a marked decrease in the past 25 years in the number of squint operations performed. Previously about 2 squint corrections were done on a typical 'general' ophthalmic operating list; now these operations are becoming something of a rarity, though increased awareness of consecutive divergence as a consequence of over-zealous squint correction has also contributed to the decline in the number of operations. The principal factors determining the onset of childhood esotropia are genetic influences, refractive errors (usually hyperopia) and a high accommodative convergence/accommodation ratio (2). The precipitating cause of a child with normal, though fragile, binocular function developing a squint has often been considered to be a systemic illness. Measles used to be common at this age - now it is rare. Whether it is the stress induced by the illness or, more specifically, a subclinical encephalitis is unknown (3), but the decline in measles and that of concomitant esotropia may be connected. Robin Finlay Consultant ophthalmic surgeon Royal United Hospital Bath BA1 3NG 1 Shann F. Editorial: A little bit of measles does you good. BMJ 1999;319:4-5. 2 Parks MM. Abnormal accommodative convergence in squint. Arch Ophthal 1958;59:364-80 3 Taylor D. Paediatric ophthalmology, Blackwell Scientific Publications, 1990;625 |
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David Emerton
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EDITOR When discussing the hypothesis that standard dose Schwartz measles vaccine reduces mortality from conditions other than measles(1) Shann refers to the observations that while measles causes only10% of child mortality the vaccine reduces mortality in developing countries by at least 30% (2) and that immunised children who have not had measles have a much lower mortality than unimmunised children who have not had measles (2,3). When I worked at Murgwanza Hospital in Tanzania from 1984-1991 measles vaccination was generally available in the community through the maternal child health programmes. These programmes included an educational component relating to nutrition, prevention of disease and early treatment of febrile illnesses such as malaria. As the primary health care programme gained momentum following the Alma Ata declaration which aimed for "health for all by the year 2000" efforts to improve health awareness intensified. It was distressing that children were not all immunised and that outbreaks of measles still occurred. Often children with measles presented late and had signs of other illnesses. We always assumed that children who were not immunised against measles when this was available were more likely to be poorly nourished and less likely to be brought for early medical care if they had life threatening illnesses such as malaria or gastro-enteritis. It is true that a study in Benin (4,2) failed to show that DTP and polio vaccination was associated with reduced mortality from other conditions . However, this study was only relevant to a narrow age band until the children were given measles vaccination. I would suggest that measles immunisation could be an indicator that parents in developing countries are trying to give their children optimum care. Therefore the improved mortality is not necessarily due to the vaccine itself. David Emerton 1 Shann F. A little bit of measles does you good. BMJ 1999;319:4-5. 2 Aaby P, Samb B, SimondonF, Coll Seck AM, KnudsenK, Whittle H. Non- specific beneficial effect of measles immunisation : analysis of mortality studies from developing countries BMJ 1995;311 481-5. 3 SambB, AaabyP, Whittle H, Coll Seck AM, Simondon F. Decline in measles case fatality ratio after the introduction of measles immunisation in rural Senegal. Am J Epidemiol 1997;145:51-7. 4 Velema JP, Alihonou EM, Gandaho T, Hounye FH Childhood mortality among users and non-users of primary health care in a rural West African community. Int J Epidemiol 1991;20,474-9. |
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Frank Shann, Director of Intensive Care Royal Children''s Hospital
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Measles immunisation causes a spectacular reduction of 30% to 86% in child mortality in developing countries (1). The benefit is greatest in the 6-12 months after immunisation, and in infancy (44% to 100%). Dr Dalton (2nd July 1999) and Dr Emerton (20th July 1999) wonder whether the apparent benefit from measles immunisation might be due to better nutrition and better health care in children who receive measles vaccine (socioeconomic confounding), rather than an effect of the vaccine. In the absence of any large randomised controlled trials of measles vaccine in developing countries, socioeconomic confounding cannot be excluded – but it is highly unlikely, for several reasons. First, in the only placebo controlled trial of measles vaccine in a developing country (2), none of the 23 vaccinated children died compared to 3 (12%) of the 25 unvaccinated children. Second, in a natural experiment in Bissau (3), some children were accidentally injected with an ineffective vaccine (given on five consecutive vaccination days over a 3 week period). There was no selection bias in this study because all the children were immunised. From the time of vaccination to 3 years of age, the mortality rate was 4.5% in 124 children who seroconverted after active vaccine and 15.1% in 53 children given ineffective vaccine. Third, in two large studies in Zaire (4) and Bangladesh (5), confounding is unlikely because measles vaccine was made available in half the study area and not in the other. The two areas had similar mortality rates before immunisation. Immunisation reduced mortality by 42% in Zaire and by 46% in Bangladesh. Fourth, studies that have controlled for socioeconomic factors have still found that measles immunisation reduced mortality by 36% to 90%(1). Fifth, measles immunisation is unlikely to be merely a marker for better health care because the reduction in mortality is greatest in the 12 months after measles immunisation (and the benefit of better health care should persist), and diphtheria-tetanus-pertussis immunisation is not associated with reduced mortality (6). Measles immunisation causes a much greater fall in mortality than the proportion of deaths attributed to measles, particularly in girls (1). Is this because measles causes many more deaths than we realise (from delayed effects of the disease, or from subclinical infection), or does the vaccine reduce mortality from conditions other than measles? The large reduction in mortality after immunisation is unlikely to be due to the prevention of delayed deaths from measles because immunised children who have not had measles have a much lower mortality than unimmunised children who have not had measles (1). Subclinical measles infection is certainly common in both immunised and unimmunised children in developing countries, however such infections have no effect on nutritional indices or mortality (7). In randomised controlled trials in Guinea-Bissau (8) and Senegal (9), children were given high-titre Edmonston-Zagreb (EZ) vaccine at 4-5 months of age or standard Schwarz vaccine at 9-10 months. In the two trials, girls given EZ vaccine had a mortality rate that was 1.95 and 1.76 times respectively that of girls given Schwarz vaccine. This occurred despite the fact that there is a good antibody response to high-titre EZ vaccine at 4-5 months, and there was no increase in measles in the EZ group. Both vaccines protected against measles, but the Schwarz vaccine also protected girls against diseases other than measles. These were both randomised trials, so socioeconomic confounding is very unlikely to be the explanation for this remarkable finding. It is crucial that the main message is not lost in the debate about cause and effect. Measles immunisation clearly causes a spectacular reduction in mortality in children in developing countries, and this effect is probably enhanced by a two-dose schedule with immunisation at 6 and 9-12 months. Far greater effort should go into seeing that all children receive measles vaccine and, if measles is ever eradicated, controlled trials will be needed to see whether the vaccine should still be given to children in countries with high child mortality rates. Frank Shann. Intensive Care Unit, Royal Children's Hospital, Melbourne, Victoria 3052, Australia Peter Aaby. Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark 1. Aaby P, Samb B, Simondon F, Seck AMC, Knudsen K, Whittle H. Non- specific beneficial effect of measles immunisation: analysis of mortality studies from developing countries. BMJ 1995;311:481-5. 2. Hartfield J, Morley D. Efficacy of measles vaccine. J Hygiene (Camb) 1963;61:143-7. 3. Aaby P, Pedersen IBR, Knudsen K, da Silva MC, Mordhorst CH, Helm- Petersen NC et al. Child mortality related to seroconversion or lack of seroconversion after measles vaccination. Pediatr Infect Dis J 1989;8:197 -200. 4. Kasongo Project Team. Influence of measles vaccination on survival pattern of 7-35-month-old children in Kasongo, Zaire. Lancet 1981;1:764- 767. 5. Koenig MA, Khan MA, Wojtyniak B, Clemens JD, Chakraborty J, Fauveau V et al. Impact of measles vaccination on childhood mortality in rural Bangladesh. Bull WHO 1990;68:441-7. 6. Velema JP, Alihonou EM, Gandaho T, Hounye FH. Childhood mortality among users and non-users of primary health care in a rural West African community. Int J Epidemiol 1991;20:474-9. 7. Bennett J, Whittle H, Samb B, Cisse B, Simondon F, Aaby P. Seroconversions in unvaccinated infants: further evidence for subclinical measles from vaccine trials in Niakhar, Senegal. Int J Epidemiol 1999;28:147-51. 8. Aaby P, Knudsen K, Whittle H, Lisse IA, Thaarup J, Poulsen A et al. Long-term survival after Edmonston-Zagreb measles vaccination in Guinea-Bissau: increased female mortality rate. J Pediatr 1993;122:904-8. 9. Aaby P, Samb B, Simondon F, Knudsen K, Seck AMC, Bennett J et al. Sex-specific differences in mortality after high-titre measles immunization in rural Senegal. Bull WHO 1994;72:761-770. |
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